Some Latino children diagnosed with acute lymphoblastic leukemia (ALL) were more likely to experience relapse than non-Hispanic white children, according to data presented at the annual meeting of the American Association for Cancer Research (AACR), held April 8-13, 2022. The study found that among patients without minimal residual disease (MRD), often considered a strong predictor of cure, relapse was more frequent in the Latino population.[1]
Acute lymphoblastic leukemia is the most common type of cancer diagnosed in children. Thanks to advances in treatment, the five-year survival rate for children diagnosed with ALL is approximately 90%.
Nevertheless, approximately 15% of children with ALL will experience a relapse, explained the study’s lead author, Philip J. Lupo, Ph.D., professor of pediatrics at Baylor College of Medicine, director of the Epidemiology and Population Sciences Program at Texas Children’s Cancer and Hematology Center, and member of the Dan L Duncan Comprehensive Cancer Center at Baylor.[1][2]
“Outcomes after relapse are much worse, with only 35% of children surviving after disease recurrence,” Lupo noted. “Additionally, poor outcomes are more common among Latinos, who are also more likely to develop ALL compared to non-Latino whites.”
Prognostic factor
Detection of minimal residual disease in the bone marrow after the first month of treatment is the strongest prognostic factor for ALL relapse. However, about half of all relapses occur in children who are MRD-negative. In this study, Lupo and colleagues sought to examine associations between MRD status and Latino ethnicity and to characterize other factors associated with relapse.[3]
The researchers examined data from the Reducing Ethnic Disparities in Acute Leukemia (REDIAL) Consortium, which includes patients diagnosed with ALL at six major pediatric cancer centers in the southwestern United States. This network of institutions aims to find what causes the observed disparities.
Study design
The study included 1,620 children diagnosed with ALL between 2004 and 2018 and included individuals who were 1-23 years of age when diagnosed with ALL. The median age at diagnosis of 5 years. The majority were Latino (60.1%) and male (56.9%).[3]
In this study, time to relapse was defined as the time from ALL diagnosis to the initial relapse event, with individuals censored at the date of death, last follow-up, or bone marrow transplant. Demographic and clinical factors evaluated included race/ethnicity (Latino, non-Latino Black, non-Latino White, non-Latino other), sex, age at diagnosis (1-5, 6-10, 11-15, >15 years), ALL immunophenotype (B-cell, T-cell), National Cancer Institute (NCI) risk group, central nervous system involvement, enrollment on a Children’s Oncology Group clinical trial, end-induction disease failure, and end-induction bone marrow flow cytometric MRD. Cox proportional hazards models were used to calculate adjusted hazards ratios (HRs) and 95% confidence intervals (CIs). Analyses were further stratified based on end-induction MRD status (positive ≥0.01%, negative <0.01%).
In all, 382 (23.5%) of the subjects were MRD-positive. Of these, 73 (19.1%) experienced a relapse, compared to 136 of 1,238 (11.0%) MRD-negative patients. Among the MRD-positive patients, Latinos were less likely to have a relapse compared to non-Latino whites. However, Latinos who were MRD-negative were about 65 percent more likely to have a relapse than non-Latino whites. This finding suggests that MRD status may not be as strong a prognostic factor in predicting the risk of relapse in Latino children with ALL compared to non-Latino whites, according to Lupo.
Among other factors identified in the study, patients who had been diagnosed with ALL after 15 years of age were nearly twice as likely to relapse as those between ages 1 and 5 years. Patients enrolled in a therapeutic clinical trial for ALL were less likely to have a relapse.
Lupo said the study highlights the importance of examining the roots of cancer health disparities.
“We were surprised that Latinos who were MRD-negative were more likely to experience ALL relapse compared to non-Latino whites,” he said.
“This highlights the need to identify factors that contribute to relapse among Latinos so that we can achieve better outcomes for children of all racial and ethnic backgrounds,” Lupo noted, adding that while MRD should still be considered as an important prognostic factor in ALL, this study indicates that it may not have the same prognostic implication across all populations.
The researchers emphasized that the outcome of their research isn’t just beneficial for Latino children with cancer, but that it may benefit all children diagnosed with ALL.
The ultimate goal is to understand the biology of leukemia and predictors of adverse outcomes in these patients. The researchers believe that this will be informative to not only children of Hispanic ethnicity but also those of any race or ethnicity.
Other ethnic disparities
The REDIAL Consortium, which includes Texas Children’s Cancer and Hematology Centers and Baylor College of Medicine, Children’s Hospital of San Antonio, Children’s UT Southwestern, Cook Children’s, Texas Tech University Health Sciences Center, Vannie E. Cook Jr. Children’s Cancer and Hematology Clinic, and Children’s Hospital of Orange County, is also continuing to research other ethnic disparities in ALL and acute myeloid leukemia. They are investigating why Latinos are more likely to develop leukemia and are also examining the frequency and risk factors that may increase the development of treatment-related toxicities.
Study limitation
Lupon and his colleagues noted that one limitation of the study, which was funded by St. Baldrick’s Foundation and the National Cancer Institute, is that the researchers did not have complete information about all factors that could have influenced relapse risk. They added that future research will incorporate other important factors into predictive models of ALL outcomes, including biological features inherent to the leukemia, inherited genetic factors, and social determinants of health.
Reference
[1] Childhood Acute Lymphoblastic Leukemia Treatment (PDQ®). Online. Last accessed on April 11, 2022.
[2] Childhood cancer. In: Howlader N, Noone AM, Krapcho M, et al., eds.: SEER Cancer Statistics Review, 1975-2010. National Cancer Institute, 2013, Section 28. Online. Last accessed on April 11, 2022.
[3] Sok P, Brown AL, Taylor OA, Bernhardt MB, Bernini JC, Erana RA, Griffin T, Heym K, Huynh VT, Klesse L, Ludwig K, Pruitt SL, Rabin KR, Scheurer ME, Lupo PJ. Disparities in relapse among a large multi-ethnic population of children diagnosed with acute lymphoblastic leukemia (ALL): A report from the Reducing Ethnic Disparities in Acute Leukemia (REDIAL) Consortium. In: Proceedings of the 113th Annual Meeting of the American Association for Cancer Research; 2021 April 8-13; New Orleans LA. Philadelphia (PA): AACR; 2022. Abstract nr 3633.
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